DNA-Based “Liquid Biopsy” Shows Promise For Early Detection of Acute Heart Transplant Rejection

New research uncovers a DNA-based “liquid biopsy” that could significantly help in saving lives and reducing health disparities. Researchers in the study successfully developed a blood test that could make the quick detection of the acute heart transplant rejection – a potentially deadly condition that occurs in the early months after a patient has received a donor heart.

The test could help in early detection, estimating it could eliminate up to 80% of invasive heart tissue biopsies that are currently used to detect rejection.

The study published in the Circulation, American Heart Association, funded by the National Heart, Lung, and Blood Institute (NHLBI), part of the National Institutes of Health.

“There’s an urgent need for an alternative method to monitor patients for acute heart transplant rejection,” said Sean Agbor-Enoh, M.D., Ph.D., study co-author and chief of the NHLBI’s Laboratory of Applied Precision Omics.

Source: Carnegie Mellon University

In the study, nearly 200 heart transplant recipients were enrolled, and the new blood test performed on them found better than tissue biopsies, as it signaled problems even when no outward signs of rejection were evident. The study showed that in their initial assessment that this ‘liquid biopsy’ is highly sensitive for acute rejection detection, finding it weeks to months before current clinical tools.

This intervention therefore could potentially save lives in the wake of a critical shortage of donor organs, says the Hannah Valantine, M.D., senior study author and the former lead investigator of the Laboratory of Organ Transplant Genomics in the Cardiovascular Branch at the NHLBI.

Moreover, according to Valantine, the professor of cardiovascular medicine at Stanford University in Palo Alto, California, this test is critical for addressing serious health disparities because African Americans tend to have higher rates of heart transplant rejection as well as they experience poorer transplant outcomes than other groups nationwide.

The test is called the donor-derived cell-free DNA test, equipped to track the DNA markers from the organ donor that appear in the blood of the transplant recipient, quoted from the study. In donor organ, the injured or dying cells, release lots of donor DNA fragments into the bloodstream relative to the normal cells.

The higher amounts of donor DNA represents a higher risk for transplant rejection in the recipient. Specialized equipment’s can be used to detect these biomarkers. Currently, tests used to detect heart transplant rejection rely on frequent and painful biopsies of heart tissue, risking potential damage to the heart and are limited by their invasiveness (ability to obtain tissue samples) and reliability for detecting acute rejection.

In the current study, the researchers found that the blood test performed better in their study than tissue biopsy. It detected higher amounts of rejection markers and earlier signs of rejection. Moreover, it also detected more instances of other types of transplant injury that can be missed by biopsy, including so-called antibody mediated rejection, one of the deadliest forms of rejection and the hardest to treat and diagnose.

The study added that the new blood test can detect rejection as early as 28 days after heart transplantation and at least three months before rejection is detectable using heart tissue biopsy.

“This test will not completely eliminate the need for invasive procedures, but it can eliminate about 80% of the biopsies currently performed after heart transplant,” said study co-author Palak Shah, M.D., a heart disease specialist at Inova Heart and Vascular Institute, Falls Church, Virginia.

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